Inhalable Alpha-1-Antitrypsin Powder for Stable Lung Delivery

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Solution Overview

Problem

Current treatments for genetic and autoimmune disorders like emphysema and COPD, such as intravenous infusion of alpha-1-antitrypsin, pose risks of virus contamination and patient compliance issues, and require cold chain distribution.

Innovation Solution

An inhalable dry powder formulation comprising recombinant alpha-1-antitrypsin protein, di-leucine, and tri-leucine, with excipients like sodium salts and non-reducing sugars, formulated into a crystalline form for improved stability and delivery via an inhaler.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If intravenous infusion of plasma-derived alpha-1-antitrypsin is used, then treatment efficacy is achieved, but risk of donor-derived virus contamination and patient compliance issues arise

Engineering Contradiction:

Improvetreatment efficacyVSAvoidvirus contamination risk

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent uses recombinant DNA technology to produce alpha-1-antitrypsin in cell culture systems, creating a molecular copy of the protein without relying on donor plasma. This eliminates the risk of donor-derived virus contamination while maintaining treatment efficacy through standardized recombinant production processes.

Inventive Principle:

Principle #26Copying

Solution Approach 2:

The patent replaces the mechanical intravenous infusion system with an inhalable dry powder formulation that can be delivered via inhaler. This substitution eliminates the need for invasive IV access, reduces patient compliance issues related to injection pain, and simplifies administration while maintaining therapeutic effectiveness.

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

2Reliability

If intravenous infusion is used for alpha-1-antitrypsin treatment, then treatment is effective, but patient compliance deteriorates due to pain and difficulty of administration

Engineering Contradiction:

Improvetreatment efficacyVSAvoidpatient compliance

Core Design Contradiction:

ReliabilityVSEase of operation

Solution Approach 1:

The patent replaces the painful and complex intravenous infusion mechanism with a simple inhalable dry powder formulation that can be administered through an inhaler. This eliminates injection-related pain and administrative complexity, significantly improving patient compliance while maintaining therapeutic efficacy through direct lung delivery.

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The patent utilizes pneumatic delivery through inhalation to transport the dry powder formulation directly to the lungs. This pneumatic delivery mechanism is non-invasive, painless, and easily complied with by patients, contrasting sharply with the mechanical IV infusion system.

Inventive Principle:

Principle #29Pneumatics and hydraulics

3Reliability

If plasma-derived alpha-1-antitrypsin is used, then treatment is effective, but cold chain distribution requirements increase logistical complexity

Engineering Contradiction:

Improvetreatment efficacyVSAvoiddistribution requirements

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent changes the physical and chemical parameters of the formulation by using recombinant protein in a dry powder form with specific excipients and force control agents. This parameter change enables the formulation to be stable at room temperature, eliminating cold chain requirements and simplifying distribution logistics while maintaining treatment efficacy.

Inventive Principle:

Principle #35Parameter changes

4Ease of operation

If recombinant alpha-1-antitrypsin in dry powder form is used, then patient compliance improves and cold chain is eliminated, but formulation stability challenges arise

Engineering Contradiction:

Improvepatient complianceVSAvoidformulation stability

Core Design Contradiction:

Ease of operationVSStability of the object's composition

Solution Approach 1:

The patent creates a composite dry powder formulation combining recombinant alpha-1-antitrypsin protein with specific excipients and force control agents (di-leucine and tri-leucine). This composite material approach enhances formulation stability by protecting the protein from aggregation and degradation while maintaining the inhalable dry powder format for improved patient compliance.

Inventive Principle:

Principle #40Composite materials

Solution Approach 2:

The patent adjusts formulation parameters including the use of force control agents at specific concentrations and the selection of appropriate excipients to optimize protein stability in dry powder form. These parameter changes ensure the formulation remains stable during storage and delivery while maintaining the benefits of inhalable administration.

Inventive Principle:

Principle #35Parameter changes

Data Source

PatentEP4433029B1Inhalable recombinant protein powder formulation for treating genetic and autoimmune disorders

Publication Date: 2026.02.18 AGENCY FOR SCI TECH & RES

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AI summary

The present invention relates to an inhalable dry powder formulation comprising a recombinant alpha-1-antitrypsin protein, a force control agent comprising di-leucine and tri-leucine in combination thereof, wherein the force control agent is present in an amount of at least 50% by weight of the formulation, and pharmaceutically acceptable excipients including a sodium salt and a non-reducing sugar or a sugar alcohol or a combination thereof.